The primary purpose of the proposed study is the relationship between folic acid and vitamin B12. The specific objectives are: 1) to study the effect of methionine on the absorption of folic acid by vitamin B12 deficient livers with a view to determine whether the mechanism resides in the effect on transport into the cell or the effect of methionine in influencing the synthesis of polyglutamates inside the cell. 2) To study the availability of folic acid in food for humans. 3) To study the synthesis of folic acid polyglutamates in liver. It has been reported that in E. coli polyglutamates can be made only from FH4 but not from 5-CH3-FH4. If this is true in mammalian tissue it could explain the effect of methionine and B12 in increasing polyglutamate levels (and thereby total folate levels) in liver, since methionine increases the proportion of FH4. Polyglutamate synthetase in liver will be purified and the role of various folic acid substrates determined. 4) To study the metabolism of folate in brain. This will involve: a) determination of the distribution of folic acid coenzymes and conjugates in brain and subcellular fractions of brain: and b) the distribution of CH3-FH4 requiring methyltransferase in brain subcellular fractions. BIBLIOGRAPHIC REFERENCES: Shane, Barry and E.L.R. Stokstad. Transport and metabolism of folates by bacteria. J. Biol. Chem. 250: 2243-2253, 1975. Shin, Y.S., E.S. Kim, J.E. Watson and E.L.R. Stokstad. Studies of folic acid compounds in nature. IV. Folic acid compounds in soybeans and cow milk. Can. J. Biochem. 53: 338-343, 1975.